rs45554035

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001131016.2(CIZ1):c.1109A>G(p.Glu370Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,613,978 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 32 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 23 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.394

Publications

5 publications found

Variant links:

Genes affected

CIZ1 (HGNC:16744): (CDKN1A interacting zinc finger protein 1) The protein encoded by this gene is a zinc finger DNA binding protein that interacts with CIP1, part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CIZ1 Gene-Disease associations (from GenCC):

dystonia 23
Inheritance: Unknown Classification: MODERATE Submitted by: Genomics England PanelApp
inherited dystonia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CIZ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002975911).

BP6

Variant 9-128179098-T-C is Benign according to our data. Variant chr9-128179098-T-C is described in ClinVar as Benign. ClinVar VariationId is 455980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00902 (1374/152322) while in subpopulation AFR AF = 0.0318 (1321/41570). AF 95% confidence interval is 0.0304. There are 32 homozygotes in GnomAd4. There are 631 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1374 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIZ1	NM_001131016.2 link	c.1109A>G	p.Glu370Gly	missense_variant	Exon 8 of 17	ENST00000372938.10	NP_001124488.1	Q9ULV3-1A0A024R885

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000372938.10 link	c.1109A>G	p.Glu370Gly	missense_variant	Exon 8 of 17	1	NM_001131016.2	ENSP00000362029.5		Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.00901

AC:

1371

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00238

AC:

592

AN:

248740

AF XY:

0.00154

show subpopulations

Gnomad AFR exome

AF:

0.0331

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000539

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000875

AC:

1279

AN:

1461656

Hom.:

Cov.:

AF XY:

0.000703

AC XY:

511

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.0322

AC:

1077

AN:

33478

American (AMR)

AF:

0.00157

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111854

Other (OTH)

AF:

0.00179

AC:

108

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

191

287

382

478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00902

AC:

1374

AN:

152322

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

631

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0318

AC:

1321

AN:

41570

American (AMR)

AF:

0.00255

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68014

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

131

196

262

327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00958

ESP6500AA

AF:

0.0250

AC:

110

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00287

AC:

348

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dystonic disorder

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

.;.;T;T;.;T;.;T;T;.

Eigen

Benign

-0.075

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.72

T;T;T;T;T;.;T;.;T;T

MetaRNN

Benign

0.0030

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;.;.;.;.;.;L;L;L;.

PhyloP100

0.39

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.8

N;.;N;.;.;N;N;N;.;N

REVEL

Benign

0.044

Sift

Uncertain

0.0020

D;.;D;.;.;D;D;T;.;T

Sift4G

Uncertain

0.035

D;D;D;D;D;D;D;D;D;T

Polyphen

0.98

D;.;D;.;.;D;D;D;D;.

Vest4

0.14

MVP

0.26

MPC

0.78

ClinPred

0.031

GERP RS

1.4

Varity_R

0.094

gMVP

0.12

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over